PMID- 28743199 OWN - NLM STAT- MEDLINE DCOM- 20180924 LR - 20180924 IS - 1556-9535 (Electronic) IS - 1556-9527 (Linking) VI - 37 IP - 2 DP - 2018 Jun TI - 3,4-Methylenedioxymethamphetamine causes cytotoxicity on 661W cells through inducing macrophage polarization. PG - 143-150 LID - 10.1080/15569527.2017.1359838 [doi] AB - The abuse of 3,4-methylenedioxymethamphetamine (MDMA), a psychedelic drug, can lead to a variety of disorders in neural system, including the death of retinal neural cells. MDMA at lower doses does not cause obvious cytotoxicity to photoreceptor cells, indicating potential indirect mechanisms which have not yet been elucidated. This study investigated the effect of MDMA at nontoxic concentration on macrophage activation state and its resultant toxicity to photoreceptor cells. Using a co-culture system, cytotoxicity was caused by MDMA on 661W cells after co-culturing with RAW264.7 macrophage. Results showed that MDMA induced the macrophages to M1 polarization, releasing more pro-inflammatory cytokines, upregulating the M1-related gene and protein expression. The phenotype, secretion pattern, and cytotoxicity of the macrophages treated by MDMA are comparable to those of the ones stimulated by IFNgamma and LPS. Our study demonstrated that MDMA promoted macrophage polarization to M1 and induced inflammatory response, providing the scientific rationale for the photoreceptor cell damage caused by the MDMA abuse. FAU - Liu, Xin AU - Liu X AD - a Department of Ophthalmology , Daqing Oil General Hospital , Daqing , People's Republic of China. FAU - Zhan, Li-Hui AU - Zhan LH AD - b Department of Ophthalmology , Daqing People's Hospital , Daqing , People's Republic of China. FAU - Sun, Xiao-Hong AU - Sun XH AD - a Department of Ophthalmology , Daqing Oil General Hospital , Daqing , People's Republic of China. FAU - Zhang, Tao AU - Zhang T AD - c Department of Ophthalmology , Secondary People's Hospital of Mudanjiang City , Mudanjiang City , People's Republic of China. FAU - Liu, Zhi-Li AU - Liu ZL AD - d Department of Opthalmology , Dashiqiao Central Hospital , Yingkou , People's Republic of China. FAU - Liang, Xiao-Fang AU - Liang XF AD - e Department of Ophthalmology , Beijing Tiantan Hospital Affiliated to the Capital Medical University , Beijing , People's Republic of China. FAU - Zhao, Fei AU - Zhao F AD - f Department of Ophthalmology , Shenyang Red Cross Hospital , Shenyang , People's Republic of China. FAU - Liu, Fang AU - Liu F AD - a Department of Ophthalmology , Daqing Oil General Hospital , Daqing , People's Republic of China. FAU - Zeng, Guang AU - Zeng G AD - a Department of Ophthalmology , Daqing Oil General Hospital , Daqing , People's Republic of China. FAU - Luan, Chun-Sheng AU - Luan CS AD - a Department of Ophthalmology , Daqing Oil General Hospital , Daqing , People's Republic of China. LA - eng PT - Journal Article DEP - 20170816 PL - England TA - Cutan Ocul Toxicol JT - Cutaneous and ocular toxicology JID - 101266892 RN - 0 (Cytokines) RN - 0 (Hallucinogens) RN - 0 (Reactive Oxygen Species) RN - 9007-43-6 (Cytochromes c) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Coculture Techniques MH - Cytochromes c/metabolism MH - Cytokines/genetics/metabolism MH - DNA Damage MH - Hallucinogens/*toxicity MH - Macrophages/*drug effects/physiology MH - Membrane Potential, Mitochondrial/drug effects MH - Mice MH - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity MH - RAW 264.7 Cells MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - 3,4-Methylenedioxymeth-amphetamine OT - 661W cells OT - inflammatory response OT - macrophage OT - photoreceptor cell damage EDAT- 2017/07/27 06:00 MHDA- 2018/09/25 06:00 CRDT- 2017/07/27 06:00 PHST- 2017/07/27 06:00 [pubmed] PHST- 2018/09/25 06:00 [medline] PHST- 2017/07/27 06:00 [entrez] AID - 10.1080/15569527.2017.1359838 [doi] PST - ppublish SO - Cutan Ocul Toxicol. 2018 Jun;37(2):143-150. doi: 10.1080/15569527.2017.1359838. Epub 2017 Aug 16.